SUSD2_HUMAN
ID SUSD2_HUMAN Reviewed; 822 AA.
AC Q9UGT4; Q9H5Y6;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Sushi domain-containing protein 2;
DE Flags: Precursor;
GN Name=SUSD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ileal mucosa;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-522.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-522.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [6]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH
RP LGALS1.
RX PubMed=23131994; DOI=10.1158/1541-7786.mcr-12-0501-t;
RA Watson A.P., Evans R.L., Egland K.A.;
RT "Multiple functions of sushi domain containing 2 (SUSD2) in breast
RT tumorigenesis.";
RL Mol. Cancer Res. 11:74-85(2013).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP C10ORF99.
RX PubMed=25351403; DOI=10.1038/srep06812;
RA Pan W., Cheng Y., Zhang H., Liu B., Mo X., Li T., Li L., Cheng X.,
RA Zhang L., Ji J., Wang P., Han W.;
RT "CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell
RT growth through inducing G1 arrest.";
RL Sci. Rep. 4:6812-6812(2014).
CC -!- FUNCTION: May be a cytokine receptor for C10ORF99. May be a tumor
CC suppressor; together with C10ORF99 has a growth inhibitory effect on
CC colon cancer cells which includes G1 cell cycle arrest
CC (PubMed:25351403). May play a role in breast tumorigenesis
CC (PubMed:23131994). {ECO:0000269|PubMed:23131994,
CC ECO:0000269|PubMed:25351403}.
CC -!- SUBUNIT: Interacts with LGALS1; leads to an increased amount of LGALS1
CC on the cell surface (PubMed:23131994). Interacts with C10ORF99; the
CC interaction is direct (PubMed:25351403). {ECO:0000269|PubMed:23131994,
CC ECO:0000269|PubMed:25351403}.
CC -!- INTERACTION:
CC Q9UGT4; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-1054721, EBI-10171774;
CC Q9UGT4; Q63HR2: TNS2; NbExp=3; IntAct=EBI-1054721, EBI-949753;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23131994,
CC ECO:0000269|PubMed:25351403}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=SUSD2 and LGALS1 co-localized in very specific,
CC punctate regions along the cell membrane of breast cancer cells.
CC {ECO:0000269|PubMed:23131994}.
CC -!- TISSUE SPECIFICITY: Highly expressed in breast cancer, but shows a
CC restricted expression pattern in normal tissues such as adipose,
CC adrenal gland, kidney, lung, mammary gland, placenta, thyroid, trachea,
CC and uterus (PubMed:23131994). Also expressed in colon; down-regulated
CC in colon cancer tissues (PubMed:25351403).
CC {ECO:0000269|PubMed:23131994, ECO:0000269|PubMed:25351403}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15481.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; Z92546; CAB62953.1; -; Genomic_DNA.
DR EMBL; AK026431; BAB15481.1; ALT_FRAME; mRNA.
DR EMBL; BC033107; AAH33107.1; -; mRNA.
DR CCDS; CCDS13824.1; -.
DR RefSeq; NP_062547.1; NM_019601.3.
DR AlphaFoldDB; Q9UGT4; -.
DR SMR; Q9UGT4; -.
DR BioGRID; 121109; 30.
DR IntAct; Q9UGT4; 5.
DR MINT; Q9UGT4; -.
DR STRING; 9606.ENSP00000351075; -.
DR GlyConnect; 1780; 6 N-Linked glycans (1 site).
DR GlyGen; Q9UGT4; 6 sites, 6 N-linked glycans (1 site), 2 O-linked glycans (2 sites).
DR iPTMnet; Q9UGT4; -.
DR PhosphoSitePlus; Q9UGT4; -.
DR BioMuta; SUSD2; -.
DR DMDM; 74735010; -.
DR EPD; Q9UGT4; -.
DR jPOST; Q9UGT4; -.
DR MassIVE; Q9UGT4; -.
DR MaxQB; Q9UGT4; -.
DR PaxDb; Q9UGT4; -.
DR PeptideAtlas; Q9UGT4; -.
DR PRIDE; Q9UGT4; -.
DR ProteomicsDB; 84263; -.
DR Antibodypedia; 284; 335 antibodies from 22 providers.
DR DNASU; 56241; -.
DR Ensembl; ENST00000358321.4; ENSP00000351075.3; ENSG00000099994.11.
DR GeneID; 56241; -.
DR KEGG; hsa:56241; -.
DR MANE-Select; ENST00000358321.4; ENSP00000351075.3; NM_019601.4; NP_062547.1.
DR UCSC; uc002zzn.2; human.
DR CTD; 56241; -.
DR DisGeNET; 56241; -.
DR GeneCards; SUSD2; -.
DR HGNC; HGNC:30667; SUSD2.
DR HPA; ENSG00000099994; Tissue enhanced (lung).
DR MIM; 615825; gene.
DR neXtProt; NX_Q9UGT4; -.
DR OpenTargets; ENSG00000099994; -.
DR PharmGKB; PA134942464; -.
DR VEuPathDB; HostDB:ENSG00000099994; -.
DR eggNOG; KOG4291; Eukaryota.
DR GeneTree; ENSGT00730000110943; -.
DR HOGENOM; CLU_019295_0_0_1; -.
DR InParanoid; Q9UGT4; -.
DR OMA; PFTISMD; -.
DR OrthoDB; 668024at2759; -.
DR PhylomeDB; Q9UGT4; -.
DR TreeFam; TF321438; -.
DR PathwayCommons; Q9UGT4; -.
DR SignaLink; Q9UGT4; -.
DR BioGRID-ORCS; 56241; 9 hits in 1067 CRISPR screens.
DR GenomeRNAi; 56241; -.
DR Pharos; Q9UGT4; Tbio.
DR PRO; PR:Q9UGT4; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9UGT4; protein.
DR Bgee; ENSG00000099994; Expressed in ileal mucosa and 131 other tissues.
DR ExpressionAtlas; Q9UGT4; baseline and differential.
DR Genevisible; Q9UGT4; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
DR GO; GO:0051782; P:negative regulation of cell division; IDA:UniProtKB.
DR CDD; cd00033; CCP; 1.
DR InterPro; IPR005533; AMOP_dom.
DR InterPro; IPR036024; Somatomedin_B-like_dom_sf.
DR InterPro; IPR001212; Somatomedin_B_dom.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR001846; VWF_type-D.
DR Pfam; PF03782; AMOP; 1.
DR Pfam; PF01033; Somatomedin_B; 1.
DR Pfam; PF00084; Sushi; 1.
DR Pfam; PF00094; VWD; 1.
DR SMART; SM00723; AMOP; 1.
DR SMART; SM00032; CCP; 1.
DR SMART; SM00216; VWD; 1.
DR SUPFAM; SSF57535; SSF57535; 1.
DR SUPFAM; SSF90188; SSF90188; 1.
DR PROSITE; PS50856; AMOP; 1.
DR PROSITE; PS00524; SMB_1; 1.
DR PROSITE; PS50958; SMB_2; 1.
DR PROSITE; PS50923; SUSHI; 1.
DR PROSITE; PS51233; VWFD; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Sushi; Transmembrane; Transmembrane helix;
KW Tumor suppressor.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..822
FT /note="Sushi domain-containing protein 2"
FT /id="PRO_0000249439"
FT TOPO_DOM 28..785
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 786..806
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 807..822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..66
FT /note="SMB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DOMAIN 285..433
FT /note="AMOP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00347"
FT DOMAIN 445..639
FT /note="VWFD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580"
FT DOMAIN 723..780
FT /note="Sushi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 522
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT DISULFID 31..44
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 31..35
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 35..62
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 42..55
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 42..44
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 48..54
FT /evidence="ECO:0000250|UniProtKB:Q9DBX3"
FT DISULFID 55..62
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 725..765
FT /evidence="ECO:0000250"
FT DISULFID 751..778
FT /evidence="ECO:0000250"
FT VARIANT 59
FT /note="R -> Q (in dbSNP:rs56289213)"
FT /id="VAR_027416"
FT VARIANT 110
FT /note="S -> T (in dbSNP:rs9680526)"
FT /id="VAR_027417"
FT VARIANT 466
FT /note="N -> S (in dbSNP:rs8141797)"
FT /id="VAR_027418"
FT CONFLICT 364
FT /note="Q -> R (in Ref. 2; BAB15481)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 822 AA; 90208 MW; 5B3E83862F045C90 CRC64;
MKPALLPWAL LLLATALGPG PGPTADAQES CSMRCGALDG PCSCHPTCSG LGTCCLDFRD
FCLEILPYSG SMMGGKDFVV RHFKMSSPTD ASVICRFKDS IQTLGHVDSS GQVHCVSPLL
YESGRIPFTV SLDNGHSFPR AGTWLAVHPN KVSMMEKSEL VNETRWQYYG TANTSGNLSL
TWHVKSLPTQ TITIELWGYE ETGMPYSQEW TAKWSYLYPL ATHIPNSGSF TFTPKPAPPS
YQRWRVGALR IIDSKNYAGQ KDVQALWTND HALAWHLSDD FREDPVAWAR TQCQAWEELE
DQLPNFLEEL PDCPCTLTQA RADSGRFFTD YGCDMEQGSV CTYHPGAVHC VRSVQASLRY
GSGQQCCYTA DGTQLLTADS SGGSTPDRGH DWGAPPFRTP PRVPSMSHWL YDVLSFYYCC
LWAPDCPRYM QRRPSNDCRN YRPPRLASAF GDPHFVTFDG TNFTFNGRGE YVLLEAALTD
LRVQARAQPG TMSNGTETRG TGLTAVAVQE GNSDVVEVRL ANRTGGLEVL LNQEVLSFTE
QSWMDLKGMF LSVAAGDRVS IMLASGAGLE VSVQGPFLSV SVLLPEKFLT HTHGLLGTLN
NDPTDDFTLH SGRVLPPGTS PQELFLFGAN WTVHNASSLL TYDSWFLVHN FLYQPKHDPT
FEPLFPSETT LNPSLAQEAA KLCGDDHFCN FDVAATGSLS TGTATRVAHQ LHQRRMQSLQ
PVVSCGWLAP PPNGQKEGNR YLAGSTIYFH CDNGYSLAGA ETSTCQADGT WSSPTPKCQP
GRSYAVLLGI IFGGLAVVAA VALVYVLLRR RKGNTHVWGA QP
